Pharmacological augmentation of endocannabinoids signaling reduces the stress response

GALLINO, SOFÍA; SURKIN, PABLO NICOLÁS; RÍOS, CARLOS EZEQUIEL; CORREA, FERNANDO; FERNÁNDEZ-SOLARI, JAVIER; DE LAURENTIIS, ANDREA

Mar del Plata

Congreso; LXI Reunión de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

Sociedad Argentina de Investigación Clínica (SAIC)

Stress activates the hypothalamic-pituitary-adrenal (HPA) axis increasing glucocorticoids and several neurotransmitters. Components of the endocannabinoid (eCB) system (ECS) are present throughout the HPA and both systems interact extensively in the regulation of stress response. The study focuses on ECS regulation of acute neurogenic stress response. Sprague-Dawley male rats were immobilized for 30 min. Each group received intracerebroventricular (icv): anandamide (AEA, 50ng/5ul), or the inhibitor of FAAH (URB597, 50ugr/5ul), or antagonists for CB1 (AM251, 500ng/5ul) or CB2 (AM630, 500ng/5ul) or vehicle 15min before stress. Others received intraperitoneal (ip) Methanandamide (2.5mg/kg), AM251 (2mg/kg), URB597 (0.3mg/kg) or vehicle. Corticosterone (CORT) by RIA and the hypothalamic nitric oxide synthase (NOS) activity were determined. Control and stressed rats were sacrificed 4hs after stress, CORT and hypothalamic and adrenal CB1, CB2 and TRPV1 mRNAs determined by PCR and qPCR. Adrenals from control rats were incubated in buffer Krebs (30 min) with ACTH (10-9M) alone or with AEA (10-9M) or URB597 (3uM) or AM251 (10-5M) or vehicle. Media CORT and tissue NOS activity were determined.Our results show that AEA blocks the increase of CORT at central and peripheral levels (p